We have previously demonstrated that patients with chest pain and normal coronary angiograms commonly have exaggerated cardiac sensitivity, with their typical pain provoked by right ventricular pacing in the absence of ischemia. In order to assess the impact of drugs used in chronic neuropathic pain syndromes, we compared imipramine 50 mg, and clonidine .2 mg to placebo in a randomized trial in 60 patients, with a one month placebo period (single blind) for all patients followed by a one month treatment period (double-blind) on imipramine, clonidine, or placebo (20 patients each group). Right ventricular pacing was repeated at the end of the treatment period. Compared to the first month on placebo, imipramine-treated patients experienced 52+25% (mean + SD) reduction in chest pain episodes (p = .03 by ANOVA) compared to a 39+51% reduction in chest pain in clonidine-treated patients and a 1+87% decrease in chest pain for placebo-treated patients. Only imipramine-treated patients demonstrated a reduction in prevalence of chest pain provoked by right ventricular pacing, from 75% off all medications to 25% on imipramine (p<.01). Thus, imipramine in relatively low doses produces a reduction in chest pain frequency in patients with chest pain and normal coronary arteries, a response that may be a consequence of visceral analgesic effects of the drug.